Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Melbourne, VIC, Australia.
FASEB J. 2021 Jun;35(6):e21639. doi: 10.1096/fj.202100435R.
During the emission phase of ejaculation, the sperm is driven from the cauda epididymidis, where it is stored, through the vas deferens by strong contractions. These contractions are thought of as being mainly induced by the sympathetic nervous system and the neurotransmitter noradrenaline. In the present study, we investigated the effect of oxytocin (suggested to exert effects during ejaculation as well) on defined segments of the rat and human epididymis using live imaging. Our results indicate that it is the very last part of the epididymis, segment 19 (S19) in rat and likewise segment 9 in human, which responds in a uniquely strong and rapid manner to oxytocin (similar to noradrenaline). Because of the complex nature of this contractile response, we developed an imaging analysis method, which allowed us to quantify multidirectional contractions and to display them using heat maps. The reaction of S19 to oxytocin was concentration-dependent and could be inhibited by pretreatment with oxytocin antagonists (atosiban and cligosiban), but not with an arginine vasopressin 1 antagonist (SR49059). In both rat and human tissue, pretreatment with the alpha-1 adrenoreceptor antagonist tamsulosin inhibited the response to noradrenaline, whereas the effect of oxytocin was unimpaired. Our data (from men and rodents) strongly suggest that the hormone oxytocin is involved in the ejaculatory process. Thus, oxytocin-based medications might be a promising non-adrenergic treatment option for ejaculatory disorders. Additionally, we propose that S19 could be an advantageous model (detecting very low concentrations of oxytocin) to test the bioactivity of new oxytocin agonists and oxytocin antagonists.
在射精的排放阶段，精子从储存精子的附睾尾部通过输精管被强烈的收缩驱动。这些收缩被认为主要是由交感神经系统和神经递质去甲肾上腺素引起的。在本研究中，我们使用活体成像技术研究了催产素（被认为在射精过程中发挥作用）对大鼠和人附睾的特定部位的影响。我们的结果表明，正是附睾的最后一部分，即大鼠的 19 段（S19）和人类的 9 段，对催产素（类似于去甲肾上腺素）产生强烈而快速的反应。由于这种收缩反应的复杂性，我们开发了一种成像分析方法，使我们能够量化多方向收缩，并使用热图显示它们。S19 对催产素的反应是浓度依赖性的，可以通过预先用催产素拮抗剂（阿托西班和克利戈西班）处理来抑制，但不能用血管加压素 1 拮抗剂（SR49059）处理。在大鼠和人组织中，预先用 α1 肾上腺素受体拮抗剂坦索罗辛处理可抑制去甲肾上腺素的反应，而催产素的作用不受影响。我们的数据（来自男性和啮齿动物）强烈表明，激素催产素参与了射精过程。因此，基于催产素的药物可能是治疗射精障碍的一种有前途的非肾上腺素能治疗选择。此外，我们提出 S19 可以作为一个有利的模型（检测非常低浓度的催产素）来测试新的催产素激动剂和催产素拮抗剂的生物活性。
